Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli

Abstract Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal...

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Main Authors: Matthew Freer, Nicole Darling, Kirsty Goncalves, Kevin J. Mills, Stefan Przyborski
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Bioengineering & Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/btm2.10484
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author Matthew Freer
Nicole Darling
Kirsty Goncalves
Kevin J. Mills
Stefan Przyborski
author_facet Matthew Freer
Nicole Darling
Kirsty Goncalves
Kevin J. Mills
Stefan Przyborski
author_sort Matthew Freer
collection DOAJ
description Abstract Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory‐like neurons that is responsive to known noxious stimuli. Through incorporation of mammalian sensory‐like neurons, we were able to recapitulate aspects of the neuroinflammatory response including secretion of substance P and a range of pro‐inflammatory cytokines in response to a well‐characterized neurosensitizing agent: capsaicin. We observed that neuronal cell bodies reside in the upper dermal compartment with neurites extending toward the keratinocytes of the stratum basale where they exist in close proximity to one another. These data suggest that we are able to model aspects of the neuroinflammatory response that occurs during exposure to dermatological stimuli including therapeutics and cosmetics. We propose that this skin construct can be considered a platform technology with a wide range of applications including screening of actives, therapeutics, modeling of inflammatory skin diseases, and fundamental approaches to probe underlying cell and molecular mechanisms.
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spelling doaj.art-31cc99ccd48e49e89dea67b44c3642a92023-05-17T07:33:11ZengWileyBioengineering & Translational Medicine2380-67612023-05-0183n/an/a10.1002/btm2.10484Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuliMatthew Freer0Nicole Darling1Kirsty Goncalves2Kevin J. Mills3Stefan Przyborski4Department of Biosciences Durham University Durham UKDepartment of Biosciences Durham University Durham UKDepartment of Biosciences Durham University Durham UKProcter & Gamble Cincinnati Ohio USADepartment of Biosciences Durham University Durham UKAbstract Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory‐like neurons that is responsive to known noxious stimuli. Through incorporation of mammalian sensory‐like neurons, we were able to recapitulate aspects of the neuroinflammatory response including secretion of substance P and a range of pro‐inflammatory cytokines in response to a well‐characterized neurosensitizing agent: capsaicin. We observed that neuronal cell bodies reside in the upper dermal compartment with neurites extending toward the keratinocytes of the stratum basale where they exist in close proximity to one another. These data suggest that we are able to model aspects of the neuroinflammatory response that occurs during exposure to dermatological stimuli including therapeutics and cosmetics. We propose that this skin construct can be considered a platform technology with a wide range of applications including screening of actives, therapeutics, modeling of inflammatory skin diseases, and fundamental approaches to probe underlying cell and molecular mechanisms.https://doi.org/10.1002/btm2.10484capsaicininflammatory cytokinesneuroinflammationneurosensitizationneurosensorialskin model
spellingShingle Matthew Freer
Nicole Darling
Kirsty Goncalves
Kevin J. Mills
Stefan Przyborski
Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli
Bioengineering & Translational Medicine
capsaicin
inflammatory cytokines
neuroinflammation
neurosensitization
neurosensorial
skin model
title Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli
title_full Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli
title_fullStr Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli
title_full_unstemmed Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli
title_short Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli
title_sort development of a mammalian neurosensory full thickness skin equivalent and its application to screen sensitizing stimuli
topic capsaicin
inflammatory cytokines
neuroinflammation
neurosensitization
neurosensorial
skin model
url https://doi.org/10.1002/btm2.10484
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